Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Neuropathological progression of clinical Parkinson disease subtypes

Nature Reviews Neurology volume 15, page 361 (2019)Cite this article

Subjects

Access through your institution
Buy or subscribe

Many attempts have been made to identify clinical subtypes of Parkinson disease (PD), but little progress has been made in determining whether they are simply a reflection of the clinical heterogeneity of PD or whether they represent different diseases hiding under one rubric. In a recent News & Views article (Clinical Parkinson disease subtyping does not predict pathology. Nat. Rev. Neurol. 15, 189–190 (2019))1, Alberto Espay and Connie Marras discussed our recent clinicopathological study showing that PD subtyping at diagnosis can provide useful information on subsequent disease progression and survival2. They stated correctly that the severity of Lewy and Alzheimer disease (AD) pathologies did not differ between the clinical subtypes but, importantly, they failed to mention that these pathological changes were reached over a considerably shorter disease duration in the diffuse malignant subgroup than in the other subtypes. This was one of the key findings of our study.

All patients with PD, despite differences in the disease course in the early and middle stages, eventually enter an accelerated terminal phase of illness, often associated with falls and cognitive impairment3,4. By the time of death, most patients with PD have reached an equivalent terminal neuropathological stage but, analogous to clinical progression, the rate of neuropathological deterioration differs among different subgroups, and it was this finding that allowed us to conclude that different neuropathologies were important determinants of clinical PD subtypes2. Despite different rates of clinical and neuropathological progression, we could not establish pathological features that would allow a neuropathologist ‘blinded’ to the clinical details to accurately categorize the clinical subtype.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Espay, A. J. & Marras, C. Clinical Parkinson disease subtyping does not predict pathology. Nat. Rev. Neurol. 15, 189–190 (2019).

    Article  Google Scholar 

  2. De Pablo-Fernandez, E. et al. Prognosis and neuropathologic correlation of clinical subtypes of Parkinson disease. JAMA Neurol. 76, 470–479 (2019).

    Article  Google Scholar 

  3. Kempster, P. A. et al. Relationships between age and late progression of Parkinson’s disease: a clinico-pathological study. Brain 133, 1755–1762 (2010).

    Article  Google Scholar 

  4. Kempster, P. A. et al. Patterns of levodopa response in Parkinson’s disease: a clinico-pathological study. Brain 130, 2123–2128 (2007).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London, UK

    Eduardo De Pablo-Fernández, Andrew J. Lees & Thomas T. Warner

  2. Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK

    Eduardo De Pablo-Fernández, Andrew J. Lees, Janice L. Holton & Thomas T. Warner

Authors
  1. Eduardo De Pablo-Fernández
    View author publications

    Search author on:PubMed Google Scholar

  2. Andrew J. Lees
    View author publications

    Search author on:PubMed Google Scholar

  3. Janice L. Holton
    View author publications

    Search author on:PubMed Google Scholar

  4. Thomas T. Warner
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Eduardo De Pablo-Fernández.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De Pablo-Fernández, E., Lees, A.J., Holton, J.L. et al. Neuropathological progression of clinical Parkinson disease subtypes. Nat Rev Neurol 15, 361 (2019). https://doi.org/10.1038/s41582-019-0197-x

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41582-019-0197-x

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing